THE ROLE OF ROSTROMEDIAL TEGMENTAL NUCLEUS IN THE REGULATION OF DOPAMINE NEURONS IN SARDINIAN ALCOHOL PREFERRING RATS

Alcoholism is a psychiatric disorder, whose aetiology involves inherited predispositions and environmental factors. Alcohol activates the brain reward circuitry, which stems from the ventral tegmental area (VTA) where dopamine (DA) cells are located. DA neuron spontaneous activity tightly depends on afferent inputs. Among these, those arising from the GABAergic rostromedial tegmental nucleus (RMTg) play a major role in controlling their impulse activity, and in mediating the effects of drugs of abuse on DA cells. In this study we took advantage of significant differences in voluntary alcohol drinking between the selectively bred Sardinian alcohol-preferring (sP) and -nonpreferring (sNP) rat lines and investigated their electrophysiological properties in vivo. Extracellular single unit recordings revealed a difference in baseline DA cell firing activity between sP and sNP rats. Accordingly, the duration of inhibition elicited by electrical stimulation of the RMTg onto DA cells was reduced in sP rats. Consistently, RMTg neurons showed a reduced spontaneous activity in sP rats. When alcohol was systemically administered, we found an increased duration of inhibition from the RMTg on DA cells in sP rats. Given the crucial role played by RMTg cells in modulating DA cell activity, and given that sP and sNP rats are phenotypes of alcohol preference and aversion, respectively, we support the key role of RMTg nucleus in the regulation of the net reward signal encoded by the reward system and suggest its involvement in the individual vulnerability to excessive alcohol drinking.